Molecular mechanism of antimutagenicity by an ethoxy-substituted phylloquinone (vitamin K1 derivative) from spinach (Spinacea oleracea L.).

Molecular mechanism of antimutagenicity by an ethoxy-substituted phylloquinone (vitamin K1 derivative) from spinach (Spinacea oleracea L.). Chem Biol Interact. 2020 Aug 15;:109216 Authors: Kumar S, Tripathi J, Srivastava AK, Gautam S Abstract In our previous study, an antimutagenic compound from spinach (Spinacea oleracea L.), ethoxy-substituted phylloquinone (ESP) was isolated and characterized. The current study deals with elucidation of the possible mechanism of antimutagenicity of ESP against ethyl methanesulfonate (EMS) deploying model systems such as human lymphoblast (TK+/-) cell line (thymidine kinase gene mutation assay) and Escherichia coli MG1655 (rifampicin resistance assay). Findings of the study ruled out the possibility of direct inactivation of EMS by ESP. DAPI competitive binding assay indicated the DNA minor groove binding activity of ESP. Interestingly, ESP did not display major groove binding or intercalating abilities. Further, proteomics study using 2-D gel electrophoresis in E. coli and subsequent studies involving single gene knockout strains revealed the possible role of tnaA (tryptophanase) and dgcP (diguanylate cyclase) genes in observed antimutagenicity. These genes have been reported to be involved in indole and cyclic-di-GMP biosynthesis, respectively, which eventually lead to cell division inhibition. In case of TK ± cell line system, ADCY genes (adenylate cyclase), a functional analogue of dgcP gene, ...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research